The Effect of Simvastatin–Ezetimibe Combination Therapy on Adipose Tissue Hormones and Systemic Inflammation in Patients with Isolated Hypercholesterolemia

Abstract

SUMMARYBackground: Pleiotropic effects of ezetimibe have only been investigated in a few studies. The aim of this article was to compare the effects of simvastatin and the combined treatment with simvastatin and ezetimibe on low-grade systemic inflammation and plasma levels of selected adipokines in patients with isolated hypercholesterolemia. Methods: The study included 69 patients with elevated cholesterol levels, who were allocated to one of the three groups treated for 12 weeks, respectively, with simvastatin (40 mg daily), simvastatin (40 mg daily) plus ezetimibe (10 mg daily), or placebo. Plasma levels of lipids, apolipoproteins, glucose homeostasis markers, leptin, adiponectin, visfatin, tumor necrosis factor-a (TNF-a), free fatty acids (FFA), and high-sensitive C-reactive protein (hsCRP) were determined on the allocation day and after 12 weeks of therapy. Results: Apart from improving lipid profile, simvastatin administered alone or in combination with ezetimibe, decreased plasma levels of hsCRP, FFA, leptin, visfatin, and TNF-a, as well as increased plasma levels of adiponectin. The combination therapy was superior to simvastatin in influencing plasma lipids/lipoproteins, hsCRP, FFA, and the investigated adipokines. The effect of the combination therapy, but not of simvastatin, on systemic inflammation and plasma adipokines was stronger in insulin-resistant than in insulin-sensitive subjects. Conclusions: The obtained results suggest that insulin-resistant patients with hypercholesterolemia and high cardiovascular risk may benefit the most from the combined treatment with simvastatin and ezetimibe.

Age may determine the effect of hypolipidemic agents on plasma adipokine levels in patients with elevated low-density lipoprotein cholesterol levels

“…In the whole population of patients, the effect of ezetimibe and simvastatin/ezetimibe combination therapy on plasma adipokines and hsCRP correlated with its impact on HOMA-IR, while the effect of ezetimibe was stronger in insulin-resistant than in insulin-sensitive subjects [21,22,24]. Correlations between adipokines or hsCRP and insulin sensitivity in ezetimibe-treated patients were also observed in both younger and older patients, analysed in the present study, but they were weak.…”

“…The study was a retrospective analysis of the previous studies of our research team [20,22,24]. The study protocol was approved by the local ethical committee, and all patients participating in the original studies gave their written informed consent before the beginning of the study.…”

“…We excluded patients with untreated stage 2 or 3 hypertension (according to the 2003 European Society of Hypertension-European Society of Cardiology guidelines), symptomatic congestive heart failure, diabetes, autoimmune disorders, acute and chronic inflammatory processes, thyroid diseases, chronic pancreatitis, impaired renal or hepatic function and body mass index more than 35 kg/m 2 , as well as patients treated within three months preceding the study with drugs interfering with statins and/or ezetimibe. During the study, all patients continued to comply with the lifestyle modification (total fat intake < 30% of total energy intake, saturated fat intake < 7% of energy consumed, cholesterol intake < 200 mg per day, an increase in fibre intake to 15 g per 1000 kcal, moderate to vigorous exercise for at least 30 minutes per day), as well as were treated with constant doses of simvastatin (40 mg, n = 23) [22], ezetimibe (10 mg, n = 21) [24], or simvastatin (40 mg) together with ezetimibe (10 mg) (n = 21) [22] for 90 days.…”

“…Atorvastatin and fenofibric acid were found to reduce adipokine release from cultures of human adipocytes [18], as well as cultures of visceral and subcutaneous adipose tissue [19]. In turn, simvastatin, administered alone or in combination with ezetimibe, decreased plasma levels of leptin, visfatin, and TNF-a and increased plasma levels of adiponectin [20][21][22], and this effect was present in both men and women [23].…”

Porównanie wpływu krótkotrwałego leczenia hipolipemicznego na stężenie adipokin w osoczu kobiet i mężczyzn z izolowaną hipercholesterolemią

“…The aim of our study was to compare the effects of 30-day treatment with two hypolipidaemic agents, atorvastatin and ezetimibe, administered alone or in combination, on plasma adipokine levels in men and women with isolated hypercholesterolaemia, participating in our previous studies [7][8][9]. The results of one study were not taken into consideration because of a longer period of treatment [10]. Leptin, adiponectin, visfatin, and TNF-a were chosen among different adipokines because they are major products of adipose tissue, playing a variety of roles in atherosclerotic plaque development and its clinical sequelae.…”